The neurotoxicity of L-DOPA, used for the treatment of Parkinsons disease, remains controversial.Although there are many reports suggesting that long-term treatment of L-DOPA causes neuronal death, an increasing body of recent evidence has proposed that L-DOPA might be neuroprotective rather than neurotoxic.The best-known potential mechanisms of 1-DOPA toxicity involve oxidative stress, including nitrosative stress and increa sed generation of neurotoxins, oxidation of 1-DOPA to quinone and semiquinone, mitochondrial dysfunction and genomic DNA damage.Glycogen synthase kinase-3 (GSK-3) affects a diverse range of biological functions controlling gene expression, cellular architecture and apoptosis.Recently, important roles of GSK-3 in 1-DOPA neurotoxicity have been suggested by studies using an endoplasmic reticulum-stressed Parkinsons disease model.To this issue, I would like to talk on the following topics: i) 1-DOPA neurotoxicity; ii) the role of GSK-3 in neuronal cell death; iii) the role of GSK-3 in 1-DOPA neurotoxicity; and iv) the development of new GSK-3 inhibitors.